|- candidate number||22986|
|- NTR Number||NTR5479|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||19-okt-2015|
|- Secondary IDs||ZonMw project number 843002633|
|- Public Title||What is the optimal treatment of a patent ductus arteriosus in preterm infants?|
|- Scientific Title||Multi-centre, randomized non-inferiority trial of early treatment versus expectative management of patent ductus arteriosus in preterm infants|
|- hypothesis||An expectative management ('watchful waiting') is not inferior regarding the composite of mortality and/or necrotising enterocolitis and/or bronchopulmonary dysplasia in comparison with an early treatment regime in preterm infants with a patent ductus arteriosus.|
|- Healt Condition(s) or Problem(s) studied||Premature infants, Patent ductus arteriosus, Neonates|
|- Inclusion criteria||- Gestational age < 28 completed weeks|
- PDA diameter > 1.5 mm
- Signed informed consent obtained from parent(s) or representative(s)
|- Exclusion criteria||- Contraindication to administration of COX-inhibitors|
- PPHN (ductal right-to-left shunting ≥ 33% of cardiac cycle)
- Congenital heart defects, other than PDA and or PFO
- Life-threatening congenital defects
- Chromosomal abnormalities and/or congenital anomalies associated with an abnormal neurodevelopmental outcome
- Use of COX-inhibitors or paracetamol prior to randomization
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jul-2016|
|- planned closingdate||14-dec-2019|
|- Target number of participants||564|
|- Interventions||Patients randomized to the expectative management arm will not receive any cyclooxygenase-inhibition and PDA management in this group can be characterized as 'watchful waiting'.|
When the patient is allocated to the medical treatment arm cyclooxygenase-inhibition is prescribed (Indomethacin or Ibuprofen). When the ductus arteriosus has remained patent after the first course of cyclooxygenase-inhibition, a second course is started.
|- Primary outcome||The composite of:|
- mortality at a postmenstrual age of <= 36 completed weeks, and/or
- necrotising enterocolitis (Bell stage >= IIa) at a postmenstrual age of <= 36 completed weeks, and/or
- bronchopulmonary dysplasia, defined as the need for supplemental oxygen at a postmenstrual age of 36 completed weeks
|- Secondary outcome||Short term sequelae of cardiovascular failure, adverse effects during the stay in the hospital and long-term neurodevelopmental consequences assessed at a corrected age of 2 years.|
|- Timepoints||Primary outcome at a postmenstrual age of <= 36 completed weeks|
Neurodevelopment at a corrected age of 2 years
|- Trial web site|| http://neonatologynetwork.eu/studies/beneductus |
|- CONTACT FOR PUBLIC QUERIES||MD PhD Willem P. de Boode|
|- CONTACT for SCIENTIFIC QUERIES||MD PhD Willem P. de Boode|
|- Sponsor/Initiator ||Radboud University Medical Center Nijmegen|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||OBJECTIVE
Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) <28 weeks. Studies have shown that the actual approach with medical and/or surgical treatment of a PDA does not reduce mortality or major neonatal morbidity. This implies that this high risk population might be over-treated with an increased iatrogenic risk of adverse effects related to the used drugs and/or surgery. An expectative approach is gaining interest, although convincing evidence is still lacking.|
An expectative management (‘watchful waiting’) is not inferior regarding the composite of mortality and/or necrotizing enterocolitis (NEC) and/or bronchopulmonary dysplasia (BPD) in comparison with an early treatment regime in preterm infants with a PDA.
Multicenter, randomized, non-inferiority study.
Preterm infants (<28 weeks) with an echocardiographically confirmed PDA with a transductal diameter >1.5 mm.
Expectative PDA management is characterized as ‘watchful waiting’. No intervention is initiated with the intention to close a PDA.
A PDA is treated with cyclooxygenase-inhibitors (COXi), which is the actual standard care in preterm infants with GA<28 weeks, and if necessary surgical ligation.
The primary outcome is the composite of mortality and/or NEC and/or BPD. Secondary outcome parameters are short term sequelae of cardiovascular failure, adverse effects during the stay in the hospital and long-term neurodevelopmental consequences assessed at an corrected age of 2 years.
SAMPLE SIZE CALCULATION
With an estimated a priori risk for the primary outcome of 35%, type I error 5%, power 80% and non-inferiority, defined as a difference between the arms <10%, a sample size of 282 patients is needed in each arm.
COST-EFFECTIVENESS ANALYSIS/ BUDGET IMPACT ANALYSIS
It is anticipated that an expectative PDA management will be cost-effective from a societal perspective with an annual budgetary saving of about €800.000, based on reduction in medical treatments and diagnostics.
|- Main changes (audit trail)|
|- RECORD||19-okt-2015 - 5-jan-2016|